XRCC5基因多态性与高发区食管癌、贲门癌遗传易感性的相关性

Correlations of XRCC5 Polymorphisms to Genetic Susceptibility to Esophageal Squamous Cell Carcinoma and Gastric Cardiac Adenocarcinoma in a High Incidence Region

背景与目的:XRCC5为DNA双链断裂修复基因,其表达异常、活性紊乱与肿瘤的发生和发展密切相关。本研究旨在探讨XRCC5基因多态性与河北省食管癌高发区-磁、涉县人群食管鳞状细胞癌(esophageal squamous cellcarcinoma,ESCC)和贲门腺癌(gastric cardiac adenocarcinoma,GCA)遗传易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测329例ESCC患者、255名GCA患者和631例健康对照人群XRCC5C74468A、G74582A单核苷酸多态性(single nucleotide polymorphisms,SNP)的基因型分布。结果:XRCC5基因C74468A C和A的等位基因频率及C/C、A/C、A/A基因型频率在ESCC、GCA及对照组之间差异无显著性(P>0.05)。根据吸烟状况和上消化道肿瘤(UGIC)家族史分层分析发现,携带A等位基因(A/C+A/A基因型)可能降低上消化道肿瘤阳性家族史人群的ESCC、GCA发病风险(经性别、年龄和吸烟校正后的OR分别为0.58和0.61,95%CI分别为0.38～0.90和0.38～0.97)。XRCC5G74582A基因G、A等位基因频率及A/A、A/G、G/G基因型频率在ESCC、GCA及对照组之间亦差异无显著性(P>0.05)。分层分析发现,携带G等位基因(A/G+G/G基因型)可能降低上消化道肿瘤阳性家族史人群的GCA发病风险(经性别、年龄和吸烟校正后的OR为0.63,95%CI为0.40～0.98)。两多态性位点联合分析显示,ESCC、GCA患者与健康对照组的单体型分布差异也无显著性(P>0.05)。结论:XRCC5C74468A A等位基因(A/C+A/A基因型)可能降低磁县和涉县上消化道肿瘤阳性家族史人群的ESCC、GCA发病风险。而G74582A G等位基因(A/G+G/G基因型)可能仅降低该地区上消化道肿瘤阳性家族史人群的GCA发病风险。

BACKGROUND ＆ OBJECTIVE： XRCC5 is a repair gene for DNA double-strand break. Its abnormal expression and dysfunction is correlated to tumorigenesis and development. This study was to investigate the correlations of XRCC5 polymorphisms to genetic susceptibility to esophageal squamous cell carcinoma （ESCC） and gastric cardiac adenocarcinoma （GCA） in a population of high incidence region, Cixian and Shexian counties of Hebei Province, China. METHODS： The genotypes of XRCC5 single nucleotide polymorphisms （SNPs）, C74468A and G74582A, in 329 ESCC patients, 255 GCA patients, and 631 healthy controls were detected by polymerase chain reaction-restrictive fragment length polymorphism （PCR-RFLP） analysis. RESULTS： The overall genotype and allelotype distributions of XRCC5 C74468A and G74582A in ESCC and GCA patients were not significantly different from those in healthy controls （P〉 0.05）. When stratified by smoking status and family history of upper gastrointestinal cancer （UGIC）, A allele （A/C ＋A/A genotype） of C74468A significantly reduced the risk of developing ESCC and GCA in positive UGIC family history group [age, sex, and smoking status adjusted odds ratios （ORs） were 0.58 and 0.61, 95% confidence intervals （CIs） were 0.38-0.90 and 0.38-0.97, respectively]; G allele （A/G ＋G/G genotype） of G74582A significantly reduced the risk of developing GCA in positive UGIC family history group （age, sex, and smoking status adjusted OR=0.63, 95% CI= 0.40-0.98）. Combined analysis of the 2 XRCC5 SNPs showed that the haplotype distribution in ESCC and GCA patients was also not significantly different from that in healthy controls （P〉 0.05）. CONCLUSIONS： In the population with positive UGIC family history in the high incidence region of Hebei Province, individuals with A allele of XRCC5 C74468A might have low risk of developing ESCC and GCA, however, individuals with G allele of XRCC5 G74582A might only have low risk of developing GCA.